Pharmaceutical Cocrystals: A Perspective on Development and Scale-up of Solution Cocrystallization

Cocrystallizationin the field of pharmaceuticals offerspromising opportunities to modify the physicochemical properties ofAPIs. However, the scaling-up of cocrystallization remains a significantchallenge. The perspective reviews these barriers and proposes a systematicdecision tree to assist researchers in a careful step-by-step approachfor scaling up cocrystal production using established solution-basedcrystallization techniques. Pharmaceutical cocrystals represent an emergent classof successfulmaterials designed based on crystal engineering principles, in whichthe limitations of the extant drugs are addressed. Though the numberof newly reported cocrystals is increasing exponentially, the scale-upof the cocrystallization process has not received enough attention.Solution cocrystallization techniques offer scalable processes thatcan utilize conventional crystallization machinery and process analyticaltechnologies. The presence of multiple components and competing kineticsof the starting materials as well as the cocrystal make the cocrystallizationprocess harder to study and control. This perspective emphasizes theimportance of multicomponent phase diagrams for identifying operatingregions in solution cocrystallization and discusses the effects ofvarious operating parameters on the process kinetics. It also coversthe intermolecular interactions involved in cocrystal development,cocrystallization methods, and quality control in pharmaceuticals.Furthermore, the role of the Design of Experiment and Quality by Designin scaling up the cocrystallization process efficiently is highlighted.A systematic decision tree has been proposed for scaling up the productionof promising cocrystals using solution-based techniques, which caneffectively address the current challenges in large-scale cocrystalproduction and help bring these potential materials to the marketin the near future.